Wilson

disease

Dr. Nawal Al-Henhena

Wilson disease

▪ Wilson disease is a disorder of copper

metabolism that occurs in roughly 1 in 30,000
individuals.

▪ It is an autosomal recessive disorder that is the

result of mutations to a copper transporter
(ATP7B gene) that resides within hepatocytes
and other cells but is more highly expressed
within hepatocytes of the liver.
Wilson disease

▪ The function of ATP7B is to move copper

from the liver into bile
▪ when it is present in excess, it be involved in
in the biosynthetic of protein ceruloplasmin
and excreted to blood.
▪ In WD biliary copper excretion is markedly
reduced.
▪ When this occurs, over time there is an
accumulation of copper within the liver and
subsequently within other tissues.
Wilson disease

This accounts for the order of the disease

manifestations in most patients
▪ liver disease first

▪ then neurologic and/or psychiatric

manifestations because of copper deposits in
central nervous system, that cause injury to
the brain.

▪ Wilson disease has a wide range of clinical

presentations, making it difficult for clinicians
to identify this disorder.
Wilson disease
Wilson Disease Pathogenesis
Wilson disease

How Does it Run in Families?

• Wilson disease is inherited in an autosomal

recessive pattern.

• Affected individuals have mutations in both

copies of ATP7B

• Carriers (mutation in only one copy) do not

have symptoms
Wilson disease

Clinical features and manifestations

• The patient starts out as an asymptomatic individual
who usually develops inflammatory progressive liver
injury with fibrosis and ultimately cirrhosis of the
liver with portal hypertension.

• At this last stage, the patient may develop

manifestations (ascites, jaundice, hepatic
encephalopathy, and, in small numbers,
hepatocellular carcinoma or cholangiocarcinoma) in
common with many patients with cirrhosis due to
other liver diseases.
Wilson disease Clinical features and manifestations

The patient may occasionally have concurrent

neurologic disease, presents as
▪ tremors,
▪ difficulty with speech
▪ dysarthria
▪ swallowing problems (due to transfer dysphasia).
▪ difficulty in gait and balance.
▪ In some patients, the neurologic manifestations may
present similar to Parkinson disease
Wilson disease Clinical features and manifestations

some of the more unusual presentations of Wilson

disease
▪ Kayser-Fleischer rings, which are cornea deposits of
copper and are one of the clinical signs of the disease
that occur in approximately 50% of patients with
hepatic presentations but in over 95% with neurologic
signs or symptoms.
▪ The other uncommon presentations are related to
psychiatric disease. There is a 1- to 2-year delay from
the onset of psychiatric and neurologic symptoms to
the time of diagnosis of Wilson disease.
Wilson disease Clinical features and manifestations

some of the more unusual presentations of

Wilson disease

▪ Movement disorder
▪ Acute liver failure
▪ Hemolytic anemia
▪ High bilirubin level and have a high indirect
bilirubin level due to hemolysis
Wilson disease Clinical features and manifestations

• Clinical spectrum • Treatment options

– Hepatic – General chelators
– Neuropsychiatric – Metallothionein
– Other inducers
• Diagnostic tests – Liver Transplantation
– Blood tests • Follow-up
– Urine tests – Blood tests
– Liver biopsy – Urine tests
– Genetic testing
Wilson disease Clinical features and manifestations

• Asymptomatic • Acute hepatitis

hepatomegaly – Similar to viral or
• Persistently autoimmune
etiologies
abnormal AST and
ALT • Acute liver failure
• Fatty liver – Coomb’s negative
hemolytic anemia
• Cirrhosis – Acute renal failure
Wilson disease Clinical features and manifestations

Kayser-Fleischer Rings
Wilson disease Clinical features and manifestations

• Coombs-negative hemolytic anemia

• Rapid progression to renal failure
• Modest rise in AST/ALT (< 2000 IU/L)
• Normal or markedly subnormal alkaline
phosphatase (< 40 IU/L)
• Serum ceruloplasmin usually decreased
• Serum and urine copper increased
Wilson disease Treatment
The Role of Diet in Wilson’s
Disease
 The Role of Diet in the
Management of Wilson Disease
• Wilson Disease cannot be managed solely with
diet
• The role of diet remains controversial
• Many physicians recommend low copper diets
during the initial stages of treatment (such as
one year)
• It is important to not excessively restrict your
diet for your entire life (quality of life issue)
The Role of Diet in the Management of Wilson Disease

Dietary Copper Consumption

• The recommended oral daily copper intake
is 0.9mg/ day1

• The average daily Western diet typically

provides 2-5mg/ day of copper

• Most dietary copper is absorbed and

excreted via secretion into bile
The Role of Diet in the Management of Wilson Disease

1. Low-copper diet:
✓ Limiting dietary copper intake is crucial for
managing Wilson disease.
✓ Foods high in copper, such as organ meats
(liver, kidney), shellfish, nuts, chocolate,
mushrooms, and legumes, should be avoided
or consumed in very small quantities.
✓ It's important to work with a registered
dietitian who specializes in Wilson disease to
develop a personalized low-copper diet plan.
The Role of Diet in the Management of Wilson Disease
The Role of Diet in the Management of Wilson Disease

2. High-zinc foods:
▪ Zinc competes with copper for absorption in
the body and can help lower copper levels.

▪ Foods rich in zinc include lean meats,

poultry, fish, whole grains, nuts and seeds
(especially pumpkin seeds), and dairy
products.

▪ Zinc supplements may also be prescribed by a

healthcare professional, but their use should
be monitored closely.
The Role of Diet in the Management of Wilson Disease

Other Foods of Concern

3. Low-copper cooking utensils:
It's important to avoid using copper
cookware or copper-lined pots and pans for
food preparation, as copper can leach into
the food during cooking.
The Role of Diet in the Management of Wilson Disease

Cookware
• Use common sense, no copper containers
or copper cookware
The Role of Diet in the Management of Wilson Disease

4.The Water Supply

• Municipal water is generally safe
• Well water or water brought through
copper pipes can be measured for copper
content
• Water purifying systems may be effective
in reducing water with a high copper
content
The Role of Diet in the Management of Wilson Disease

5. Fresh fruits and vegetables:

▪ Most fruits and vegetables are generally low in

copper and can be included in the diet.

▪ However, it's essential to check with a

healthcare professional or dietitian regarding
specific fruits and vegetables that may need to be
limited due to their copper content.
The Role of Diet in the Management of Wilson Disease

▪ Adequate protein intake: Consuming adequate

protein is important for overall health.

▪ Vitamin supplementation: Additional vitamins

and minerals, such as vitamin E, selenium, and
vitamin C, are required to support liver health
and reduce oxidative stress.

▪ Vitamin and mineral supplementation should be

done under the guidance of a healthcare
professional.
The Role of Diet in the Management of Wilson Disease

▪ Regular monitoring:

Regular monitoring of copper levels in

the blood and urine is essential to
evaluate the effectiveness of dietary
modifications and treatment.
The Role of Diet in the Management of Wilson Disease

Role of Dietician Consultation

• Consultation with a dietician is advisable
for practicing vegetarians1

• Consultation should be considered:

– during the initial year of therapy
– at any time if patient quality of life issues
arise

1Roberts EA and Schilsky ML. AASLD Practice Guidelines, 2008

The Role of Diet in the Management of Wilson Disease

Copper Deficiency
• Deficiency may cause;
• Neutropenia
• Impaired bone calcification
• And hypochromic anemia not responsive
to iron supplements.
The Role of Diet in the Management of Wilson Disease

Maintenance Therapy with Zinc

• 50 mg elemental zinc 3 times a day
• Take 30 minutes before meals
• 220 mg of zinc sulfate
• May cause gastric irritation
• If not tolerated, zinc gluconate
• Zinc is not to be given at the same time as
penicillamine or trientine
• Allow 5 hours between doses
Summary: The role of diet in Wilson
Disease
• Wilson Disease cannot be managed solely with
diet
• Dietary copper restriction should be considered
during the initial phase of therapy
• Wilson Disease patients can enjoy a relatively
normal diet throughout their life
• Dietician consultation is advised for vegetarians
and should be considered in all patients
Thank
You